Miniaturized three dimensional (3D) organ or organoid culture systems are of increasing academic and economic interest. These 3D culture systems are aimed to allow investigation of how organs work and behave under certain stimuli as well as to test the effect of chemical compounds or compositions on particular organs or groups thereof and to study the pharmacokinetic behaviour of such compounds or compositions. In particular with regard to safety testing of chemical compounds, alternatives are required to replace animal experiments and to generate data which can more easily be used to efficiently and reliably predict safety in humans. The quality of such an in vitro 3D culture system will depend on its ability to reflect as closely as possible the physiological function and environment of the respective organ or organoid. This goal can only be achieved if the organs are not considered as separate, independent objects but if the complexity of interaction between different organs in an organism is mimicked as closely as possible. In order to allow for generation of meaningful data, it is required that the culture system remains stable for a prolonged period of time. However, most of the known 3D culture systems known today reflect only one cell type or model only one type of organ or organoid. 3D culture systems which take into account multiple organs and which allow dynamic culture of these multiple organs have only recently been described.
In WO2009/146911 A2 an organ-on-a-chip device has been presented. This organ-on-a-chip device is designed to be self-contained and sensor controlled. The device allows establishing or maintaining organs or organoids as well as stem cell niches in a miniaturized chip format. The organ-on-a-chip device can comprise a multiplicity of organ growth sections comprising an organ or organoid, a medium feed reservoir and a medium waste reservoir functionally connected to each other such that the organs or organoids of the organ growth section can be fed with medium from the medium feed reservoir and that degradation products and waste can be disposed via the medium waste reservoir. Although this model allows the simultaneous culture of more than one organ on one chip, this device does not allow for interaction and cross-talk between different organs on the chip. Furthermore, this device does not reflect all functions necessary to achieve homeostasis of the culture system over a prolonged period of time.
In WO 2012/016711 A1 a 3D cell culture model is presented comprising one or more organ growth sections, a self-contained circulation system configured to supply organs or organoids cultured in the organ growth sections with nutrients and a extra-capillary fluid or waste collector to collect interstitial fluid and degradation products from the organ growth sections. This system allows for simultaneous culture of more than one organ and mimics a vascular system supplying and interconnecting the different organs. Thus, this system allows for interaction and cross-talk between the organs or organoids of the system. However, this device does not reflect all functions necessary to achieve homeostasis of the culture system over a prolonged period of time.